Using Type 2 Diabetes Medications to Treat T1D

Robert Busch, MD: We have many type 2 diabetes medications that our colleagues utilize in type 1 diabetes. This may be off-label use, so I’ll first address what we do for adults with type 2 diabetes, and then I’ll look at adults with type 1 diabetes. For obese patients with type 1 diabetes, we might give a GLP1 [receptor agonist] because we’re comfortable giving that in patients with type 2 diabetes. Of course, we have to decrease the amount of insulin the patient is getting, depending on what their baseline A1C [glycated hemoglobin] is. The GLP1s have often been used for their glycemic benefit, by lowering glucagon—not for increasing endogenous insulin, because there isn’t any, but for other aspects like lowering appetite and delaying stomach emptying. But the cardiovascular benefits in patients with type 2 diabetes haven’t been tested for type 1 diabetes, necessarily. I know that Novo Nordisk was doing a large study with semaglutide in patients with type 1 diabetes, and many of our colleagues have done that. In the pediatric world, Dr Quattrin, do you use any of the off-label type 2 diabetes drugs in patients with type 1 diabetes?

Teresa Quattrin, MD: I can talk about my practice and that of my colleagues. First, a brief word on pramlintide, which is an analog 2 beta cell peptide 2 amylin treated with insulin. It’s administered together with insulin at meals. It’s the only drug that’s approved, and the insulin should be adjusted to decrease the risk of hypoglycemia. Honestly, in our very large population, we’re not administering this routinely. Many of us have used metformin—I did many years ago—based on a small, open-label study. I found the same results that have been found in a proper double-blind study, which is that metformin showed some improvement in the lipid panels in adults and cohorts. Ultimately, it didn’t improve the glycemic control.

In a way, GLP1 [receptor agonists] are the holy grail. In terms of studies done prospectively and that are double blind, there has been a decrease in daily insulin dose and body weight. Body weight has become a real issue and a potential comorbidity of type 1 diabetes. Once upon a time, this was a disease for which we weren’t administering insulin well, and we administered it for patients who were too big. But now between 12% and 54% of adults, depending on different papers, are obese. One of 3 adolescents are overweight and obese. It seems that this drug makes sense for them, but pediatrics would be an off-label administration in type 1 diabetes.

With the SGLT2 inhibitors, in a properly prospective randomized study they showed some improvement in glycemic control. But extensive counseling has to be implemented because they can increase the risk of euglycemic diabetic ketoacidosis [DKA].

Robert Busch, MD: In adults with type 2 diabetes, GLP1s and SGLT2s have benefits other than glycemic. We’re using a lot of SGLT2s in patients with type 2 diabetes, for renal protection, and in patients with heart failure. When we have a patient with type 1 diabetes who has heart failure or kidney disease with proteinuria, we’re doing that gingerly because of the euglycemic DKA with SGLT2. GLP1s have atherosclerotic heart disease benefit by lowering stroke and MI [myocardial infarction] stroke death. We’ve carried that over to some of our patients with type 1 diabetes as well. It’s off-label.

What about the higher-dose liraglutide, the 3-mg dose, that’s approved for weight reduction in teenagers? Earlier you mentioned the STEP TEENS trial. If high-dose semaglutide is approved, do you think you’ll be utilizing those tools there?

Teresa Quattrin, MD: We’ve done some small, open-label pilot studies on that. It’s a tool that we may utilize in the future, but I want to be careful not to give the message, at least in my opinion, that we’re ready to use it now. Having said that, my other research interest is patients who are overweight and obese. Given what we know in terms of the alleles and the genetic predisposition to that, the combination of obesity and type 1 diabetes leads to insulin resistance. That also occurs with exogenous insulin. Moreover, 1 of the pitfalls of subcutaneous insulin delivery is that it cannot restore intraportal levels of insulin-like growth factor 1, which is important for insulin sensitivity. We pediatricians are very conservative, but my hope is that we’ll have something to address that issue.

Kimberly Simmons, MD, MPH/MSPH: One other thing that’s interesting is that once somebody is diagnosed with type 1 diabetes, they may have presented as type 2 diabetes had they not gotten type 1 diabetes. Not looking at the family history, especially in the pediatric population, and the overall picture can be a limitation to providing the best care possible.

Robert Busch, MD: If it weren’t for the beta cell being destroyed, they would have had type 2 diabetes, but the beta cell got knocked out beforehand by the type 1 diabetes.

Teresa Quattrin, MD: To that point, we should encourage our pediatricians in physical exams to focus on signs like acanthosis nigricans—I hate this Greek or Latin name—the darkening on the skin that these kids have. Yes, there are many people mistaken as type 2 diabetes. Now the data are showing that type 1 diabetes is extremely frequent. There are data from the United Kingdom that are alarming, showing that type 1 diabetes is extremely frequent, more than we thought in adults. Many people are going to be misdiagnosed and should be diagnosed correctly.

Robert Busch, MD: What about immunosuppressive and immunomodulatory agents? This is an autoimmune disease. Dr Goland, what has been done with those agents?

Robin S. Goland, MD: We’ve talked a little about the TrialNet study. Teplizumab, the drug that was recently approved by the FDA, was first evaluated in new-onset type 1 diabetes and then impaired glucose tolerance type 1 prediabetes, through the auspices of TrialNet. Other immunomodulating agents, such as rituximab, abatacept, a few other agents, and ATG, have been shown to be effective in preserving beta cell function. With other immunomodulatory agents, I recommend that they be considered in type 1 diabetes outside a trial, but anyone with positive antibodies or new-onset diabetes should be counseled to consider a trial because this is an incredible time. The science is exploding. There’s a lot of reason for hope and optimism. This is a time of opportunity for people with new-onset diabetes.

Transcript Edited for Clarity